Synthetic oligonucleotides recruit ILF2/3 to RNA transcripts to modulate splicing.
Synthetic oligonucleotides recruit ILF2/3 to RNA transcripts to modulate splicing.
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DOI：
10.1038/nchembio.939
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发表时间：
2012-04-15
影响因子：
14.8
通讯作者：
Bennett, C. Frank
中科院分区：
文献类型：
--
作者：
Rigo, Frank;Hua, Yimin;Chun, Seung J.;Prakash, Thazha P.;Krainer, Adrian R.;Bennett, C. Frank
我们描述了一种新的技术，通过选择性识别与化学修饰的反义寡核苷酸（ASO）形成的异源双链体，招募特定的蛋白质RNA。通常，ASO通过与其RNA靶标杂交并阻断单链RNA结合蛋白的结合来发挥作用。出乎意料的是，我们发现具有2′-脱氧-2 ′-氟（2′-F）核苷酸但不具有其他2′化学修饰的ASO具有额外的性质：它们与RNA形成异源双链体，这些RNA被白细胞介素增强子结合因子2和3复合物（ILF 2/3）特异性识别。2′-F ASO介导的IL F2/3向RNA的募集可以通过调节靶转录物的选择性剪接来控制基因表达。在细胞培养物和小鼠中，ILF 2/3募集到外显子附近的前体mRNA导致外显子从成熟mRNA中缺失。我们讨论了使用化学工程的ASO，招募特定的蛋白质来调节基因表达的治疗干预的可能性。
We describe a new technology for recruiting specific proteins to RNA through selective recognition of heteroduplexes formed with chemically modified antisense oligonucleotides (ASOs). Typically, ASOs function by hybridizing to their RNA targets and blocking the binding of single-stranded RNA–binding proteins. Unexpectedly, we found that ASOs with 2′-deoxy-2′-fluoro (2′-F) nucleotides, but not with other 2′ chemical modifications, have an additional property: they form heteroduplexes with RNA that are specifically recognized by the interleukin enhancer-binding factor 2 and 3 complex (ILF2/3). 2′-F ASO–directed recruitment of ILF2/3 to RNA can be harnessed to control gene expression by modulating alternative splicing of target transcripts. ILF2/3 recruitment to precursor mRNA near an exon results in omission of the exon from the mature mRNA, both in cell culture and in mice. We discuss the possibility of using chemically engineered ASOs that recruit specific proteins to modulate gene expression for therapeutic intervention.
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影响因子：
64.5
作者：
Cooper TA;Wan L;Dreyfuss G
通讯作者：
Dreyfuss G
DOI：
10.1073/pnas.95.15.8514
发表时间：
1998-07-21
影响因子：
11.1
作者：
Liao, HJ;Kobayashi, R;Mathews, MB
通讯作者：
Mathews, MB
影响因子：
11.4
作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
通讯作者：
CROWTHER, RA
影响因子：
46.9
作者：
Goraczniak, Rafal;Behlke, Mark A.;Gunderson, Samuel I.
通讯作者：
Gunderson, Samuel I.
影响因子：
10.5
作者：
Hua, Yimin;Sahashi, Kentaro;Krainer, Adrian R.
通讯作者：
Krainer, Adrian R.